Soman and VX: different effect on cellular signalling

Abstract

Summary The purpose of our study was to examine the early expression of p21 and activated transcription factors ATF-2, CREB, Elk-1, p53 after soman and VX poisoning, to throw light on the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman (60 μg.kg −1 ‐ 70% LD 50 ) or VX (8 μg.kg −1 ‐ 70% LD 50 ). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-ATF-2 Thr-69/71 , phospho-CREB Ser-133 , phospho-Elk-1 Ser-383 , phospho-p53 Ser-15 , and protein p21 expressions were measured using computer Image analysis in apical and cryptal enterocytes of the colon transversum. After soman poisoning, we observed an increased phospho-CREB in cryptal enterocytes 4, 24, and 72 h after poisoning, while apical enterocytes expressed increased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and 24 h after soman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were not changed 4, 24, and 72 h after soman poisoning. VX poisoning did not change any of measured parameters. Soman and VX showed a different effect on cellular signalling. Soman seems to cause additional effects, which are not related to the basic mechanism of nerve agent-induced toxicity and which temporarily suppress promitotic pathways of proliferating cells and persist in cells during the differentiation process.